An Approach to Analyzing and Predicting Force-extension Curves of Nucleic Acids

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dc.contributor.authorAfanasyev, Alexanderen
dc.contributor.committeechairOnufriev, Alexeyen
dc.contributor.committeememberLiu, Shixinen
dc.contributor.committeememberBatra, Romesh C.en
dc.contributor.committeememberWayne, Jennifer Susanen
dc.contributor.departmentEngineering Science and Mechanicsen
dc.date.accessioned2023-07-28T08:04:31Zen
dc.date.available2023-07-28T08:04:31Zen
dc.date.issued2023-07-27en
dc.description.abstractSingle-molecule stretching experiments reveal a distinct plateau region in force-extension curves of nucleic acids such as long double-stranded deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). The dissertation comprises two parts. In the first part, we propose an approach to help analyze polymer force-extension curves that exhibit a distinct plateau region. When coupled to a bead-spring dynamic model, the approach qualitatively reproduces a variety of experimental force-extension curves of long double-stranded (ds) DNA and RNA, including torsionally constrained and unconstrained DNA, and negatively supercoiled DNA. In the plateau region of the force-extension curves, our molecular dynamics simulations show that the polymer separates into a mixture of slightly and highly stretched states without forming macroscopically distinct phases. In the second part, we hypothesize that, depending on the sequence composition, multiple distinct plateau regions can be seen in force-extension curves of long dsDNA fragments under physiological solvent conditions. We explore specific long double-stranded DNA sequences where we expect the phenomenon to occur, and to characterize the distribution of states along the polymer. Our molecular dynamics simulations show that multi-plateau regions are observed in the force-extension curves of specific long double-stranded DNA fragments. The formation of mixed states of slightly and highly stretched DNA, co-existing with macroscopically distinct phases in several segments in the plateau regions, is also predicted.en
dc.description.abstractgeneralSingle-molecule stretching experiments reveal a distinct plateau region in force-extension curves of nucleic acids such as long double-stranded DNA and RNA. In this dissertation, we propose a simple bead-spring dynamic model that qualitatively reproduces a variety of experimental force-extension curves of long double-stranded DNA and RNA that exhibit a distinct plateau region. Based on the model, we make multiple predictions. In particular, we predict that multiple distinct plateau regions can be seen in force-extension curves of long composite double-stranded DNA fragments under physiological solvent conditions. We believe our findings should be of interest to both experimentalists and theoreticians. Experimentalists might find our model useful for routine analysis of force-extension curves of double-stranded DNA and RNA. Theoreticians may appreciate our general approach.en
dc.description.degreeDoctor of Philosophyen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:37342en
dc.identifier.urihttp://hdl.handle.net/10919/115898en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectDNAen
dc.subjectRNAen
dc.subjectMolecular Dynamicsen
dc.titleAn Approach to Analyzing and Predicting Force-extension Curves of Nucleic Acidsen
dc.typeDissertationen
thesis.degree.disciplineEngineering Mechanicsen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.nameDoctor of Philosophyen

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